Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)
研究概览
简要总结
Phase II trial to study the effectiveness of homoharringtonine in treating patients who have chronic phase chronic myelogenous leukemia. Drugs used in chemotherapy, such as homoharringtonine, work in different ways to stop cancer cells from dividing so they stop growing or die
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of homoharringtonine in patients with transformed phases of chronic myelogenous leukemia (CML). (Phase I completed as of 2/11/2004.) II. Determine the toxicity profile of this drug in these patients. III. Determine the response duration in patients with chronic phase CML treated with this drug.
IV. Compare the pharmacokinetics of this drug administered as a continuous infusion vs subcutaneously in these patients.
OUTLINE: This is a pilot, dose-escalation study. (Phase I completed as of 2/11/2004.)
Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic phase chronic myelogenous leukemia (CML), as defined by the following:
- •Less than 15% blasts in the peripheral blood (PB) or bone marrow (BM)
- •Less than 20% basophils in the PB or BM
- •Platelet count > 100,000/mm^3 (unless related to therapy)
- •Absence of clonal evolution*
- •Philadelphia chromosome- OR BCR/ABL-positive disease by cytogenetics, fluorescence in situ hybridization, or polymerase chain reaction
- •Failed prior therapy with imatinib mesylate, as defined by any of the following:
- •Failed to achieve or have lost a complete hematologic remission after 3 months of therapy
- •Failed to achieve or have lost at least a minimal cytogenetic response after 6 months of therapy
- •Failed to achieve or have lost a major or complete cytogenetic response after 12 months of therapy
- •Unable to tolerate imatinib mesylate despite adequate dose adjustment
- •Failed no more than 2 prior treatment regimens (in addition to imatinib mesylate)
- •Treatment with hydroxyurea is not considered one regimen
- •Ineligible for known regimens or protocols of higher efficacy or priority
- •Performance status - Zubrod 0-2
- •At least 2 months
- •Bilirubin no greater than 2.0 mg/dL
- •Creatinine less than 2.0 mg/dL
- •No New York Heart Association class III or IV heart disease
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
排除标准
- 未提供
研究组 & 干预措施
Treatment (omacetaxine mepesuccinate)
Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.
Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.
干预措施: omacetaxine mepesuccinate (Drug)
Treatment (omacetaxine mepesuccinate)
Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.
Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (omacetaxine mepesuccinate)
Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.
Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)
时间窗: 14 days
Complete hematologic remission (CHR) defined as at least 4 weeks of bone marrow (less than 5% blasts) and peripheral blood with WBC < 10 x 10^9/L and no peripheral blasts, promyelocytes, or myelocytes
时间窗: Up to 6 years
Using a Bayesian approach.
次要结局
未报告次要终点